A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil.
Identifieur interne : 001401 ( Main/Corpus ); précédent : 001400; suivant : 001402A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil.
Auteurs : David J. Heal ; Niki W. Buckley ; Jane Gosden ; Nigel Slater ; Charles P. France ; David HackettSource :
- Neuropharmacology [ 1873-7064 ] ; 2013.
English descriptors
- KwdEn :
- Animals (MeSH), Benzhydryl Compounds (pharmacology), Cocaine (pharmacology), Dextroamphetamine (pharmacology), Discrimination, Psychological (drug effects), Dose-Response Relationship, Drug (MeSH), Drug Evaluation, Preclinical (MeSH), Female (MeSH), Lisdexamfetamine Dimesylate (MeSH), Methylphenidate (pharmacology), Modafinil (MeSH), Rats (MeSH), Reinforcement, Psychology (MeSH), Self Administration (MeSH).
- MESH :
- chemical , pharmacology : Benzhydryl Compounds, Cocaine, Dextroamphetamine, Methylphenidate.
- drug effects : Discrimination, Psychological.
- Animals, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Female, Lisdexamfetamine Dimesylate, Modafinil, Rats, Reinforcement, Psychology, Self Administration.
Abstract
Lisdexamfetamine dimesylate, which consists of L-lysine covalently bound to D-amfetamine, is the first prodrug for treating ADHD. Its metabolic conversion to yield D-amfetamine by rate-limited, enzymatic hydrolysis is unusual because it is performed by peptidases associated with red blood cells. Other stimulants shown to be effective in managing ADHD include D-amfetamine, methylphenidate and modafinil. All have the potential for misuse or recreational abuse. The discriminative and reinforcing effects of these compounds were determined in rats using a 2-choice, D-amfetamine (0.5 mg/kg, i.p.)-cued drug-discrimination test, and by substitution for intravenous cocaine in self-administration. Lisdexamfetamine (0.5-1.5 mg/kg [D-amfetamine base], p.o.) generalised to saline when tested 15 min post-dosing, but dose-dependently generalised to d-amfetamine at 60 min. At 120 min, its D-amfetamine-like effects were substantially diminished. At 15 min, methylphenidate (3.0-10 mg/kg, p.o.) and D-amfetamine (0.1-1.5 mg/kg, p.o.) dose-dependently generalised to the intraperitoneal D-amfetamine cue. Switching to the intraperitoneal route reduced the interval required for lisdexamfetamine to be recognised as D-amfetamine-like, but did not alter its potency. Switching to intraperitoneal injection increased the potency of methylphenidate and D-amfetamine by 3.4× and 2.2×, respectively. Modafinil (50-200 mg/kg, i.p.) generalised partially, but not fully, to d-amfetamine. Methylphenidate (0.1, 0.3, 1.0 mg/kg/injection, i.v.) maintained robust self-administration at the 2 highest doses. Neither lisdexamfetamine (0.05, 0.15 or 0.5 mg/kg/injection [D-amfetamine base], i.v.) nor modafinil (0.166, 0.498 or 1.66 mg/kg/injection, i.v.) served as reinforcers. The results reveal important differences between the profiles of these stimulants. Lisdexamfetamine did not serve as a positive reinforcer in cocaine-trained rats, and although it generalised fully to D-amfetamine, its discriminative effects were markedly influenced by its unusual pharmacokinetics.
DOI: 10.1016/j.neuropharm.2013.05.021
PubMed: 23748096
Links to Exploration step
pubmed:23748096Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil.</title><author><name sortKey="Heal, David J" sort="Heal, David J" uniqKey="Heal D" first="David J" last="Heal">David J. Heal</name><affiliation><nlm:affiliation>RenaSci Ltd, BioCity Nottingham, Pennyfoot Street, Nottingham NG1 1GF, UK. david.heal@renasci.co.uk</nlm:affiliation></affiliation></author><author><name sortKey="Buckley, Niki W" sort="Buckley, Niki W" uniqKey="Buckley N" first="Niki W" last="Buckley">Niki W. Buckley</name></author><author><name sortKey="Gosden, Jane" sort="Gosden, Jane" uniqKey="Gosden J" first="Jane" last="Gosden">Jane Gosden</name></author><author><name sortKey="Slater, Nigel" sort="Slater, Nigel" uniqKey="Slater N" first="Nigel" last="Slater">Nigel Slater</name></author><author><name sortKey="France, Charles P" sort="France, Charles P" uniqKey="France C" first="Charles P" last="France">Charles P. France</name></author><author><name sortKey="Hackett, David" sort="Hackett, David" uniqKey="Hackett D" first="David" last="Hackett">David Hackett</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="RBID">pubmed:23748096</idno><idno type="pmid">23748096</idno><idno type="doi">10.1016/j.neuropharm.2013.05.021</idno><idno type="wicri:Area/Main/Corpus">001401</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001401</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil.</title><author><name sortKey="Heal, David J" sort="Heal, David J" uniqKey="Heal D" first="David J" last="Heal">David J. Heal</name><affiliation><nlm:affiliation>RenaSci Ltd, BioCity Nottingham, Pennyfoot Street, Nottingham NG1 1GF, UK. david.heal@renasci.co.uk</nlm:affiliation></affiliation></author><author><name sortKey="Buckley, Niki W" sort="Buckley, Niki W" uniqKey="Buckley N" first="Niki W" last="Buckley">Niki W. Buckley</name></author><author><name sortKey="Gosden, Jane" sort="Gosden, Jane" uniqKey="Gosden J" first="Jane" last="Gosden">Jane Gosden</name></author><author><name sortKey="Slater, Nigel" sort="Slater, Nigel" uniqKey="Slater N" first="Nigel" last="Slater">Nigel Slater</name></author><author><name sortKey="France, Charles P" sort="France, Charles P" uniqKey="France C" first="Charles P" last="France">Charles P. France</name></author><author><name sortKey="Hackett, David" sort="Hackett, David" uniqKey="Hackett D" first="David" last="Hackett">David Hackett</name></author></analytic><series><title level="j">Neuropharmacology</title><idno type="eISSN">1873-7064</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Benzhydryl Compounds (pharmacology)</term><term>Cocaine (pharmacology)</term><term>Dextroamphetamine (pharmacology)</term><term>Discrimination, Psychological (drug effects)</term><term>Dose-Response Relationship, Drug (MeSH)</term><term>Drug Evaluation, Preclinical (MeSH)</term><term>Female (MeSH)</term><term>Lisdexamfetamine Dimesylate (MeSH)</term><term>Methylphenidate (pharmacology)</term><term>Modafinil (MeSH)</term><term>Rats (MeSH)</term><term>Reinforcement, Psychology (MeSH)</term><term>Self Administration (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Benzhydryl Compounds</term><term>Cocaine</term><term>Dextroamphetamine</term><term>Methylphenidate</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Discrimination, Psychological</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Dose-Response Relationship, Drug</term><term>Drug Evaluation, Preclinical</term><term>Female</term><term>Lisdexamfetamine Dimesylate</term><term>Modafinil</term><term>Rats</term><term>Reinforcement, Psychology</term><term>Self Administration</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lisdexamfetamine dimesylate, which consists of L-lysine covalently bound to D-amfetamine, is the first prodrug for treating ADHD. Its metabolic conversion to yield D-amfetamine by rate-limited, enzymatic hydrolysis is unusual because it is performed by peptidases associated with red blood cells. Other stimulants shown to be effective in managing ADHD include D-amfetamine, methylphenidate and modafinil. All have the potential for misuse or recreational abuse. The discriminative and reinforcing effects of these compounds were determined in rats using a 2-choice, D-amfetamine (0.5 mg/kg, i.p.)-cued drug-discrimination test, and by substitution for intravenous cocaine in self-administration. Lisdexamfetamine (0.5-1.5 mg/kg [D-amfetamine base], p.o.) generalised to saline when tested 15 min post-dosing, but dose-dependently generalised to d-amfetamine at 60 min. At 120 min, its D-amfetamine-like effects were substantially diminished. At 15 min, methylphenidate (3.0-10 mg/kg, p.o.) and D-amfetamine (0.1-1.5 mg/kg, p.o.) dose-dependently generalised to the intraperitoneal D-amfetamine cue. Switching to the intraperitoneal route reduced the interval required for lisdexamfetamine to be recognised as D-amfetamine-like, but did not alter its potency. Switching to intraperitoneal injection increased the potency of methylphenidate and D-amfetamine by 3.4× and 2.2×, respectively. Modafinil (50-200 mg/kg, i.p.) generalised partially, but not fully, to d-amfetamine. Methylphenidate (0.1, 0.3, 1.0 mg/kg/injection, i.v.) maintained robust self-administration at the 2 highest doses. Neither lisdexamfetamine (0.05, 0.15 or 0.5 mg/kg/injection [D-amfetamine base], i.v.) nor modafinil (0.166, 0.498 or 1.66 mg/kg/injection, i.v.) served as reinforcers. The results reveal important differences between the profiles of these stimulants. Lisdexamfetamine did not serve as a positive reinforcer in cocaine-trained rats, and although it generalised fully to D-amfetamine, its discriminative effects were markedly influenced by its unusual pharmacokinetics.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23748096</PMID><DateCompleted><Year>2014</Year><Month>08</Month><Day>13</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-7064</ISSN><JournalIssue CitedMedium="Internet"><Volume>73</Volume><PubDate><Year>2013</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Neuropharmacology</Title><ISOAbbreviation>Neuropharmacology</ISOAbbreviation></Journal><ArticleTitle>A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil.</ArticleTitle><Pagination><MedlinePgn>348-58</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.neuropharm.2013.05.021</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0028-3908(13)00235-9</ELocationID><Abstract><AbstractText>Lisdexamfetamine dimesylate, which consists of L-lysine covalently bound to D-amfetamine, is the first prodrug for treating ADHD. Its metabolic conversion to yield D-amfetamine by rate-limited, enzymatic hydrolysis is unusual because it is performed by peptidases associated with red blood cells. Other stimulants shown to be effective in managing ADHD include D-amfetamine, methylphenidate and modafinil. All have the potential for misuse or recreational abuse. The discriminative and reinforcing effects of these compounds were determined in rats using a 2-choice, D-amfetamine (0.5 mg/kg, i.p.)-cued drug-discrimination test, and by substitution for intravenous cocaine in self-administration. Lisdexamfetamine (0.5-1.5 mg/kg [D-amfetamine base], p.o.) generalised to saline when tested 15 min post-dosing, but dose-dependently generalised to d-amfetamine at 60 min. At 120 min, its D-amfetamine-like effects were substantially diminished. At 15 min, methylphenidate (3.0-10 mg/kg, p.o.) and D-amfetamine (0.1-1.5 mg/kg, p.o.) dose-dependently generalised to the intraperitoneal D-amfetamine cue. Switching to the intraperitoneal route reduced the interval required for lisdexamfetamine to be recognised as D-amfetamine-like, but did not alter its potency. Switching to intraperitoneal injection increased the potency of methylphenidate and D-amfetamine by 3.4× and 2.2×, respectively. Modafinil (50-200 mg/kg, i.p.) generalised partially, but not fully, to d-amfetamine. Methylphenidate (0.1, 0.3, 1.0 mg/kg/injection, i.v.) maintained robust self-administration at the 2 highest doses. Neither lisdexamfetamine (0.05, 0.15 or 0.5 mg/kg/injection [D-amfetamine base], i.v.) nor modafinil (0.166, 0.498 or 1.66 mg/kg/injection, i.v.) served as reinforcers. The results reveal important differences between the profiles of these stimulants. Lisdexamfetamine did not serve as a positive reinforcer in cocaine-trained rats, and although it generalised fully to D-amfetamine, its discriminative effects were markedly influenced by its unusual pharmacokinetics.</AbstractText><CopyrightInformation>Copyright © 2013 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Heal</LastName><ForeName>David J</ForeName><Initials>DJ</Initials><AffiliationInfo><Affiliation>RenaSci Ltd, BioCity Nottingham, Pennyfoot Street, Nottingham NG1 1GF, UK. david.heal@renasci.co.uk</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Buckley</LastName><ForeName>Niki W</ForeName><Initials>NW</Initials></Author><Author ValidYN="Y"><LastName>Gosden</LastName><ForeName>Jane</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Slater</LastName><ForeName>Nigel</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>France</LastName><ForeName>Charles P</ForeName><Initials>CP</Initials></Author><Author ValidYN="Y"><LastName>Hackett</LastName><ForeName>David</ForeName><Initials>D</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>06</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Neuropharmacology</MedlineTA><NlmUniqueID>0236217</NlmUniqueID><ISSNLinking>0028-3908</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001559">Benzhydryl Compounds</NameOfSubstance></Chemical><Chemical><RegistryNumber>207ZZ9QZ49</RegistryNumber><NameOfSubstance UI="D008774">Methylphenidate</NameOfSubstance></Chemical><Chemical><RegistryNumber>I5Y540LHVR</RegistryNumber><NameOfSubstance UI="D003042">Cocaine</NameOfSubstance></Chemical><Chemical><RegistryNumber>R3UK8X3U3D</RegistryNumber><NameOfSubstance UI="D000077408">Modafinil</NameOfSubstance></Chemical><Chemical><RegistryNumber>SJT761GEGS</RegistryNumber><NameOfSubstance UI="D000069478">Lisdexamfetamine Dimesylate</NameOfSubstance></Chemical><Chemical><RegistryNumber>TZ47U051FI</RegistryNumber><NameOfSubstance UI="D003913">Dextroamphetamine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001559" MajorTopicYN="N">Benzhydryl Compounds</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003042" MajorTopicYN="N">Cocaine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003913" MajorTopicYN="N">Dextroamphetamine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004192" MajorTopicYN="N">Discrimination, Psychological</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004353" MajorTopicYN="N">Drug Evaluation, Preclinical</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000069478" MajorTopicYN="N">Lisdexamfetamine Dimesylate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008774" MajorTopicYN="N">Methylphenidate</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000077408" MajorTopicYN="N">Modafinil</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012054" MajorTopicYN="Y">Reinforcement, Psychology</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012646" MajorTopicYN="N">Self Administration</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">ADHD</Keyword><Keyword MajorTopicYN="N">AMF</Keyword><Keyword MajorTopicYN="N">C(max)</Keyword><Keyword MajorTopicYN="N">C-II</Keyword><Keyword MajorTopicYN="N">C-IV</Keyword><Keyword MajorTopicYN="N">CD</Keyword><Keyword MajorTopicYN="N">DAT</Keyword><Keyword MajorTopicYN="N">Discriminative effects</Keyword><Keyword MajorTopicYN="N">Drug discrimination</Keyword><Keyword MajorTopicYN="N">FR</Keyword><Keyword MajorTopicYN="N">IACUC</Keyword><Keyword MajorTopicYN="N">IR</Keyword><Keyword MajorTopicYN="N">Institutional Animal Care and Use Committee</Keyword><Keyword MajorTopicYN="N">Lisdexamfetamine</Keyword><Keyword MajorTopicYN="N">Methylphenidate</Keyword><Keyword MajorTopicYN="N">Modafinil</Keyword><Keyword MajorTopicYN="N">PET</Keyword><Keyword MajorTopicYN="N">PFC</Keyword><Keyword MajorTopicYN="N">Reinforcer</Keyword><Keyword MajorTopicYN="N">SAL</Keyword><Keyword MajorTopicYN="N">SR</Keyword><Keyword MajorTopicYN="N">Schedule 2 Controlled Drug</Keyword><Keyword MajorTopicYN="N">Schedule 4 Controlled Drug</Keyword><Keyword MajorTopicYN="N">Self-administration</Keyword><Keyword MajorTopicYN="N">amfetamine</Keyword><Keyword MajorTopicYN="N">attention deficit hyperactivity disorder</Keyword><Keyword MajorTopicYN="N">controlled drug</Keyword><Keyword MajorTopicYN="N">d-Amfetamine</Keyword><Keyword MajorTopicYN="N">dopamine reuptake transporter</Keyword><Keyword MajorTopicYN="N">fixed ratio</Keyword><Keyword MajorTopicYN="N">i.p.</Keyword><Keyword MajorTopicYN="N">i.v.</Keyword><Keyword MajorTopicYN="N">immediate release</Keyword><Keyword MajorTopicYN="N">intraperitoneal</Keyword><Keyword MajorTopicYN="N">intravenous</Keyword><Keyword MajorTopicYN="N">maximum plasma drug concentration</Keyword><Keyword MajorTopicYN="N">p.o.</Keyword><Keyword MajorTopicYN="N">per os (oral)</Keyword><Keyword MajorTopicYN="N">positron emission tomography</Keyword><Keyword MajorTopicYN="N">prefrontal cortex</Keyword><Keyword MajorTopicYN="N">saline</Keyword><Keyword MajorTopicYN="N">sustained release</Keyword><Keyword MajorTopicYN="N">t(max)</Keyword><Keyword MajorTopicYN="N">time to reach maximum plasma drug concentration</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2012</Year><Month>12</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2013</Year><Month>04</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2013</Year><Month>05</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>6</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>6</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>8</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23748096</ArticleId><ArticleId IdType="pii">S0028-3908(13)00235-9</ArticleId><ArticleId IdType="doi">10.1016/j.neuropharm.2013.05.021</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/AutomedicationFrancoV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001401 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 001401 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= AutomedicationFrancoV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= pubmed:23748096
|texte= A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Corpus/RBID.i -Sk "pubmed:23748096" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a AutomedicationFrancoV1
| This area was generated with Dilib version V0.6.38. |  |